Lorigerlimab

MacroGenics局势崩坏至此？ 该公司联合创始人、总裁兼首席执行官Scott Koenig正在计划离职。 日前，MacroGenics宣布了领导层交接，Scott Koenig计划在明年初辞去总裁兼首席执行官的职位。不过Scott Koenig将继续作为MacroGenics的顾问和股东。 受到该消息的影响，MacroGenics的股价反而出现小幅度上涨。 管线一款接一款失败 MacroGenics成立于2000年，是老牌抗体公司。基于其DART 、TRIDENT等技术平台，公司与赛诺菲、吉利德、Incyte、再鼎医药、天境生物等公司建立了重要的合作关系，单抗和双抗管线大多进行了授权转让。 不过平台技术的安全性验证遭遇不小挑战。特别是公司重点押注的B7H3靶点，单抗，双抗产品皆这折戟于不良事件。 2019年1月，FDA叫停了CD3/B7H3双抗MGD009针对B7H3阳性实体瘤的临床I期试验，因为该临床出现了肝脏不良事件。目前公司官网已无该管线信息。 2022年7月，B7H3单抗MGA271一项治疗复发难治性头颈鳞癌的II期临床试验被MacroGenic宣布停止，原因是该临床出现了11.3%的死亡事件（62名患者中7人死亡），可能与出血事件有关。 2024年8月，B7H3 ADC药物Vobramitamab Duocarmazine（MGC-018）的II期临床TAMARACK被MacroGenic宣布停止，原因是TAMARACK试验中发生了5例患者死亡事件。不过该B7H3 ADC联合lorigerlimab（PD-1×CTLA-4 DART分子）的1/2期剂量递增研究继续患者招募，并计划于今年晚些时候进行剂量扩展研究。 延伸阅读：B7H3 ADC毒性累积 此外，2024年3月，艾伯维终止了与MacroGenics在ADAM9 ADC上的合作，因为临床I期数据未达预期。 目前，MacroGenics重点管线有三款，分别是处于早期临床的B7H3 ADC MGC026和PD-1×CTLA-4 DART分子lorigerlimab，以及临床前的ADAM9 ADC  MGC028。 管线一款接着一款的失败，也就算了，毕竟管线开发失败乃是兵家常事。可难受的，还有缺钱的窘境，以及管线持续烧钱的现况。 缺钱的窘境 MacroGenics共开发了三款商业化产品，分别是MARGENZA、ZYNYZ、TZIELD。 ZYNYZ和TZIELD早早的被授权出去，并为MacroGenics带来了不菲的收入，但是架不住MacroGenics花钱快啊。 根据MacroGenics发布的2024年第二季度财报，公司季度净亏损5570万美元。 截止第二季度，现金流只剩下1.4亿美元的MacroGenics，也有些着急了。 打包出售MARGENZA MARGENZA（Margetuximab）是一款HER2单抗，于2020年获FDA批准，用于治疗转移性HER2+乳腺癌患者。 值得注意的是，再鼎曾在2018年引进了Margetuximab，Margetuximab于2023年9月获得中国药监局批准，不过由于再鼎并未启动商业化运营，MacroGenics无法拿到其里程碑款项。今年早些时候，再鼎终止了与MacroGenics关于Margetuximab合作，协议已于2024年5月14日生效。 MARGENZA在MacroGenics自己商业化运营下，销售情况惨淡。根据MacroGenics发布的2024年第二季度财报，产品季度净销售额约为525万美元。 如果产品不赚钱，就及时卖掉回血。 2024年10月，MacroGenics将MARGENZA打包出售给TerSera Therapeutics LLC。根据协议条款，TerSera将以4000万美元的前期付款+3500万美元的里程碑付款获得MARGENZA的全球权利。 相较于MARGENZA的营收，说不上是卖了一个好价钱，但起码让MacroGenics回笼了一笔资金。 指望Incyte的里程碑打款 ZYNYZ（retifanlimab）是一款PD-1单抗，于2017年授权给Incyte。ZYNYZ于2023年3月23日首次获得FDA批准，用于治疗转移性或复发局部晚期默克尔细胞癌（MCC）成人患者。 根据Incyte公司财报，ZYNYZ在今年前六个月的销售额仅为100万美元。 延伸阅读：FDA加速批准PD-1单抗一线治疗默克尔细胞癌 MacroGenics与Incyte于2024年7月达成协议，宣布已经实现与retifanlimab开发进度相关的1亿美元里程碑。 此外，MacroGenics还有资格从Incyte获得高达 2.1亿美元的剩余开发和监管里程碑，以及高达3.3亿美元的潜在商业里程碑。以及，MacroGenics从Incyte获得该产品全球净销售额的15%至24%的分层特许权使用费。 TZIELD早就被卖了 TZIELD（teplizumab）是一款CD3单抗，于2018年授权给了Provention Bio。TZIELD于2022年11月获得FDA批准，用于预防/延缓1型糖尿病。 2023年3月，赛诺菲以约29亿美元收购了Provention Bio，获得了TZIELD。 延伸阅读：1型糖尿病百年首个革命性疗法，CD3单抗终获批 MacroGenics原本还拥有TZIELD的专利权，能够获得TZIELD全球净销售额的个位数专利使用费。 但是由于MacroGenics等不及这笔权益慢慢变现，直接就在2024年3月将Tzield的专利权以1亿美元的预付款出售给了药物专利权收购公司DRI Healthcare Trust。 小结 MacroGenics共开发了三款商业化产品，但三款产品现在都不属于MacroGenics了。 作为技术公司，不善商业操作，将管线授权出去也是一种优选择。但是MacroGenics孵化了三款商业化产品，手握专利权，按理来说，应该是躺下收钱了。 参考资料： 1.https://ir.macrogenics.com/news-releases/news-release-details/macrogenics-announces-leadership-transition 2.https://ir.macrogenics.com/news-releases/news-release-details/macrogenics-provides-update-corporate-progress-second-quarter 本周好文推荐 如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

Scott Koenig, M.D., Ph.D., to step down as President and CEOBoard to initiate search process to identify new CEO ROCKVILLE, MD, Oct. 30, 2024 (GLOBE NEWSWIRE) -- MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, today announced that Scott Koenig, M.D., Ph.D., intends to step down as President and Chief Executive Officer early next year. The Company’s Board of Directors has retained Heidrick & Struggles to lead a search process to identify its next Chief Executive Officer and has established a special committee of the Board to oversee the transition process. William Heiden, Chairman of the Board of Directors said, “Scott was a co-founder of MacroGenics twenty-four years ago and the Company has achieved many milestones under his leadership – including several partnered or company-owned FDA approved monoclonal antibody therapeutics developed by the company. On behalf of the Board, I want to thank Scott for his incredible dedication to the Company’s mission of discovering and developing novel therapeutics to improve patient care.” Mr. Heiden continued, “Today, MacroGenics has several innovative antibody-based therapeutics in development for the treatment of cancer, as well as significant alliances with leading pharmaceutical and biotechnology companies to develop and commercialize novel therapeutics. The Company today has a broad portfolio of promising assets and a strong balance sheet, and the Board and Scott agreed that this is the right time to transition to our next phase of leadership. We look forward to continuing to benefit from his perspectives as an advisor and shareholder.” “I am proud of our many achievements since our founding in 2000, in which we built a fully integrated, science-focused biotechnology company and have been successful in discovering, developing, manufacturing, and commercializing novel immunotherapeutics derived from our proprietary Fc-engineered antibody, bi-specific DART molecule, and antibody drug conjugate (ADC) technologies,” said Dr. Koenig. “Since the company’s IPO in 2013, we were able to fund a significant part of the development portfolio through the achievement of over $1 billion of non-dilutive capital via partnerships. Thanks to the incredible passion and dedication of the people at MacroGenics, three novel therapeutics from our pipeline advanced to approval, including MARGENZA® and ZYNYZ® to treat patients with cancer, and TZIELD® for individuals with early-stage Type 1 diabetes, and we have advanced a rich portfolio of clinical and preclinical molecules in development. I am confident that MacroGenics is well positioned in its current mission to address the significant unmet medical needs of patients with cancer. I look forward to continuing to support the Company in its work to achieve its key strategic objectives and create value for all our stakeholders.” About MacroGenics, Inc. MacroGenics is a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer. The Company generates its pipeline of product candidates primarily from its proprietary suite of next-generation antibody-based technology platforms, which have applicability across broad therapeutic domains. The combination of MacroGenics' technology platforms and protein engineering expertise has allowed the Company to generate promising product candidates and enter into several strategic collaborations with global pharmaceutical and biotechnology companies. For more information, please see the Company's website at www.macrogenics.com. MacroGenics, the MacroGenics logo and MARGENZA are trademarks or registered trademarks of MacroGenics, Inc. Cautionary Note on Forward-Looking Statements Any statements in this press release about future expectations, plans and prospects for MacroGenics (“Company”), including statements about the Company’s strategy, future operations, clinical development of and regulatory plans for the Company’s therapeutic candidates, expected timing of the release of final safety and efficacy data, including mature median rPFS and other statements containing the words “subject to”, "believe", “anticipate”, “plan”, “expect”, “intend”, “estimate”, “potential,” “project”, “may”, “will”, “should”, “would”, “could”, “can”, the negatives thereof, variations thereon and similar expressions, or by discussions of strategy constitute forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: risks that TZIELD, vobramitamab duocarmazine, lorigerlimab, ZYNYZ, MARGENZA or any other product candidate’s revenue, expenses and costs may not be as expected, risks relating to TZIELD, vobramitamab duocarmazine, lorigerlimab, ZYNYZ, MARGENZA or any other product candidate’s market acceptance, competition, reimbursement and regulatory actions; future data updates, especially timing and results of mature median radiographic progression-free survival, other efficacy and safety data with respect to vobramitamab duocarmazine; our ability to provide manufacturing services to our customers; the uncertainties inherent in the initiation and enrollment of future clinical trials; the availability of financing to fund the internal development of our product candidates; expectations of expanding ongoing clinical trials; availability and timing of data from ongoing clinical trials; expectations for the timing and steps required in the regulatory review process; expectations for regulatory approvals; expectations of future milestone payments; the impact of competitive products; our ability to enter into agreements with strategic partners and other matters that could affect the availability or commercial potential of the Company's product candidates; business, economic or political disruptions due to catastrophes or other events, including natural disasters, terrorist attacks, civil unrest and actual or threatened armed conflict, or public health crises; costs of litigation and the failure to successfully defend lawsuits and other claims against us; and other risks described in the Company's filings with the Securities and Exchange Commission. In addition, the forward-looking statements included in this press release represent the Company's views only as of the date hereof. The Company anticipates that subsequent events and developments will cause the Company's views to change. However, while the Company may elect to update these forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so, except as may be required by law. These forward-looking statements should not be relied upon as representing the Company's views as of any date subsequent to the date hereof. ###